A number of advanced cancers such as renal cell carcinoma and squamous cell carcinoma of the lung have proven particularly refractory to chemotherapy. It is therefore warranted to test new agents or new experimental modalities in these tumors. Animal studies suggest that the chemotherapeutic activity of certain alkylating agents can be augmented by the use of oral dimethylsulfoxide (DMSO). Patients with metastatic renal cell carcinoma or squamous cell carcinoma were therefore tested with DMSO and alkylating agents. Fifteen patients with renal cell carcinoma were treated with DMSO in water and thiotepa. There were no objective responses and DMSO and thiotepa were not useful in this disease. Four patients with squamous cell lung cancer have been started on DMSO plus cyclophosphamide. There have been no objective anti-tumor responses seen in the first patients, but it is too early to determine overall activity of this combination.